Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In eukaryotic cells, secretory proteins and glycoproteins migrate from the rough endoplasmic reticulum, their site of synthesis, through Golgi vesicles before being released from the cell. Cellular and viral integral plasma membrane glycoproteins are co-translationally inserted into the rough endoplasmic reticulum membrane and follow a similar pathway to the cell surface. Previous studies using endoglycosidase H (Endo H) suggested that in rat hepatoma cells the vesicular stomatitis virus (VSV) G protein, albumin and transferrin migrate from the rough endoplasmic reticulum to the Golgi apparatus at different rates. Here we show directly that in human hepatoma HepG2 cells, five secreted proteins mature from the rough endoplasmic reticulum to Golgi vesicles at characteristic rates which differ at least threefold. The results are incompatible with bulk-phase movement of the luminal contents of the endoplasmic reticulum, and suggest that there is a membrane-bound receptor that selectively mediates the transport of secretory proteins from the rough endoplasmic reticulum to the Golgi.
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PMID:Hepatoma secretory proteins migrate from rough endoplasmic reticulum to Golgi at characteristic rates. 686 94

Endogenous processing of viral glycoproteins for presentation to CD4+T cells is a poorly investigated aspect of antigen processing and presentation. This pathway may involve not only pathogens, but also self proteins, and may thus be involved in self-tolerance. We have characterized the processing of the endoplasmic reticulum-restricted glycoprotein (G) of vesicular stomatitis virus, termed poison tail (Gpt), biochemically and enzymatically, and by T cell recognition assays. Expressed with a vaccinia vector, Gpt remains endoglycosidase H-sensitive and does not mature to endoglycosidase D sensitivity. The protein is degraded in the ER with a T1/2 of 4 h. Gpt peptides are not secreted since Gpt-infected cells are unable to sensitize uninfected antigen-presenting cells in an innocent bystander assay. Using flow cytometry, Gpt is undetectable on the plasma membrane; in contrast, wild-type G is readily found on the surface or secreted into the milieu as soluble G following infection of A20 cells with a vaccinia recombinant expressing G. The degradation of Gpt is sensitive to the thiol reagent diamide and occurs optimally at physiological pH. A series of proteolytic inhibitors were tested: 3,4-dichloroisocoumarin and 1-chloro-3-tosylamido-7-amino-2-heptanone inhibited degradation, which suggests the involvement of a serine protease. The degradation does not require transport to the Golgi complex, and is not sensitive to a variety of lysosomotropic agents. We show that the degradation products include the immunogenic epitopes recognized by a panel of T cell clones and hybridomas.
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PMID:Processing of a viral glycoprotein in the endoplasmic reticulum for class II presentation. 766 84

Bafilomycin A1 (Baf), a specific inhibitor of the vacuolar-type proton pump, inhibited the entry of Semliki Forest virus and vesicular stomatitis virus into BHK-21 cells. The inhibition occurred at concentrations that dissipated intracellular acidic compartments. Viral infection was totally inhibited by 30 nM Baf while endocytosis of the virus or fluorescein isothiocyanate-dextran was not affected. Thus, a vacuolar-type proton pump was responsible for acidification of the endosomes needed for virus entry. When the cells were exposed to 100 nM Baf after virus entry, viral glycoprotein synthesis continued normally. The viral glycoproteins acquired resistance to endoglycosidase H, indicating arrival in the medial Golgi apparatus. However, maturation processes occurring in the trans-Golgi compartment were inhibited, and the amounts of viral glycoproteins appearing at the cell surface were reduced. Double immunofluorescence studies showed that in the presence of Baf the viral glycoproteins were found in and around mannosidase II-positive Golgi structures. To analyze whether Baf blocked transport from the trans-Golgi compartment to the cell surface, the viral glycoproteins were allowed to accumulate in the trans-Golgi network by utilizing a 20 degrees C block. Subsequent incubation at 37 degrees C in the presence of Baf did not inhibit the terminal maturation processes or transport to the cell surface, suggesting that the block was before the trans-Golgi network. These results indicate that an active vacuolar-type proton pump in the Golgi apparatus is essential for protein transport in BHK-21 cells.
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PMID:Active vacuolar H+ATPase is required for both endocytic and exocytic processes during viral infection of BHK-21 cells. 802 Dec 66

Folimycin (concanamycin A) specifically inhibited vacuolar-type ATPase as far as examined. Folimycin blocked excretion of the glycoprotein (G protein) of vesicular stomatitis virus into the medium and, instead, G protein was accumulated intracellularly. The intracellularly accumulated G protein electrophoresed a little faster than mature one. The N-glycan of the G protein was endoglycosidase H-sensitive, and terminal galactose and N-acetylglucosamine were not detected essentially on sequential digestion with exoglycosidases, indicating that processings known to occur in the Golgi apparatus do not take place in the presence of folimycin. The oligosaccharide chain of the G protein was determined to have a composition of Man8GlcNAc2 as analyzed by Bio-Gel P-4 column chromatography and high-performance liquid chromatography following digestion with alpha- and then with beta-mannosidase. Activities of mannosidase I and glycosyltransferases prepared from baby hamster kidney cells were not inhibited as far as examined, indicating that the incompleteness of the N-glycosidic chain in folimycin-treated cells is not caused by inhibition of processing enzymes. Taken together these observations suggest that folimycin blocks the intracellular translocation of G protein before the step of trimming by mannosidase I which is confined to the cis compartment of the Golgi. The intracellular localization of G protein as revealed by fluorescence microscopy was in good accordance with this assumption.
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PMID:Folimycin (concanamycin A), a specific inhibitor of V-ATPase, blocks intracellular translocation of the glycoprotein of vesicular stomatitis virus before arrival to the Golgi apparatus. 824 93

Microinjection of antibodies against a synthetic peptide of a non-clathrin-coated vesicle-associated coat protein, beta-COP, blocks transport of a temperature-sensitive vesicular stomatitis virus glycoprotein (ts-O45-G) to the cell surface. Transport is inhibited upon release of the viral glycoprotein from temperature blocks at 39.5 degrees C (endoplasmic reticulum [ER]) and 15 degrees C (intermediate compartment), but not at 20 degrees C (trans-Golgi network). Ts-O45-G is arrested in tubular membrane structures containing p53 at the interface of the ER and the Golgi stack. This is consistent with inhibition of acquisition of endoglycosidase H resistance of ts-O45-G in injected cells. Secretion of endogenous proteins and maturation of cathepsin D are also inhibited. These data provide in vivo evidence that beta-COP has an important function in biosynthetic membrane traffic in mammalian cells.
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PMID:Beta-COP is essential for biosynthetic membrane transport from the endoplasmic reticulum to the Golgi complex in vivo. 833 7

Using the glycoprotein of the tsO45 mutant of vesicular stomatitis virus (VSV-G) as a marker, we have developed a system capable of measuring vesicular transport from the endoplasmic reticulum (ER) to the trans Golgi network (TGN) in vitro. Movement from the ER to the cis Golgi compartment was assessed by the conversion of VSV-G from a totally endoglycosidase D (endo D)-resistant form to a species containing one endo D-resistant and one endo D-sensitive oligosaccharide (GD1). Similarly, delivery to the medial cisternae was measured by the appearance of the completely endo D-sensitive form of VSV-G (GD2) or by the acquisition of complete resistance to endoglycosidase H (endo H) (GHr) and delivery to the TGN by the appearance of an endo H-resistant form of VSV-G which was sensitive to digestion with neuraminidase and subsequently beta-galactosidase (GHt). Movement between each sequential compartment required ATP and soluble proteins (cytosol) and was inhibited by nonhydrolyzable analogues of GTP and by an antibody toward the N-ethylmaleimide-sensitive factor NSF. In contrast, fractionation of the cytosol by ammonium sulfate precipitation indicated that distinct proteins were required for movement between successive compartments. Similarly, inclusion of a mutant form of the small molecular weight GTP-binding protein rab1A inhibited movement between the ER and cis Golgi, and between the cis and medial cisternae, but did not affect transport from the medial Golgi to the TGN. Conversely, the protein kinase inhibitor staurosporine prevented movement between the medial Golgi and the TGN but did not influence transport between the ER and early Golgi compartments. This study provides the first demonstration that vesicular transport between the ER and TGN can be reconstituted in a cytosol-dependent fashion in vitro, allowing a direct analysis of the roles of individual components in multiple transport events.
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PMID:Differential inhibition of multiple vesicular transport steps between the endoplasmic reticulum and trans Golgi network. 838 97

Megalomicin (MGM) is a macrolide antibiotic which has been demonstrated previously to cause an anomalous glycosylation of viral proteins. Here we show that MGM produces profound alterations on Golgi morphology and function. The addition of MGM at 50 microM for 1 h caused a dilation of the Golgi detected by immunofluorescence staining for medial- and trans-Golgi markers. The effect of MGM was clearly more intense on the trans-side of the Golgi, as evidenced in electron microscope preparations. The effect on Golgi morphology was reversible and correlated with an impairment of glycoprotein processing in the trans-Golgi. Thus, although the vesicular stomatitis virus G protein was processed in the presence of MGM to an endoglycosidase H-resistant form, it was poorly sialylated. The sialylation of cellular proteins was also inhibited, resulting in cells with low level of sialylation on the cell surface. However MGM did not inhibit the activities of the galactosyl- or sialyltransferase as measured in vitro. MGM inhibited cis- to medial-, and more strongly, medial- to trans-Golgi transport of vesicular stomatitis virus G protein in an in vitro system, suggesting that the impairment in glycoprotein maturation observed in vivo is the result of intra-Golgi transport inhibition.
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PMID:Intra-Golgi transport inhibition by megalomicin. 863 86

We have infected isolated skeletal muscle fibers with the vesicular stomatitis virus or the mutant tsO45, whose glycoprotein is blocked in the endoplasmic reticulum at 39 degrees C. Immunofluorescence analysis for the viral glycoprotein indicated that the fibers were infected over their entire length at a virus dose of 10(9)/ml. When we infected the myofibers with the tsO45 mutant at 39 degrees C, the viral glycoprotein appeared to be localised to the terminal cisternae of the sarcoplasmic reticulum. Upon shifting the cultures to the permissive temperature, 32 degrees C, in the presence of dinitrophenol, which blocks vesicular transport, the viral glycoprotein proceeded to completely fill the sarcoplasmic reticulum. Thus, both the endoplasmic reticulum located at the terminal cisternae of the sarcoplasmic reticulum, and the entire endoplasmic and sarcoplasmic reticulum appeared to be continuous. Shifting the culture temperature from 39 degrees C to 20 degrees C, resulted in prominent perinuclear staining throughout the fibers, accompanied by the appearance of distinct bright dots between the nuclei. Electron microscopic immunoperoxidase labeling indicated that these bright structures represented the Golgi apparatus. When either the tsO45-infected or wild-type virus-infected fibers were incubated at 32 degrees C, the viral glycoprotein showed a staining pattern that consisted of double rows of punctate fluorescence. Immunogold labeling showed that the viral glycoprotein was present in both the transverse tubules as well as the endoplasmic/sarcoplasmic reticulum endomembranes. In addition, extensive viral budding was observed in the transverse tubules. Metabolic labeling experiments revealed that only half of the glycoprotein was processed in the Golgi, and this processed form had become incorporated into the budding viral particles. Thus, the processed viral glycoprotein was targeted to the transverse tubules. The other half of the glycoprotein remained endoglycosidase H-sensitive, suggesting its retention in the endoplasmic/sarcoplasmic reticulum endomembranes.
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PMID:Transport pathway, maturation, and targetting of the vesicular stomatitis virus glycoprotein in skeletal muscle fibers. 879 45

The influence of protein kinase A activity on transport of newly synthesized vesicular stomatitis virus G glycoprotein along the exocytic pathway was examined. Transport of vesicular stomatitis virus G glycoprotein to the cell surface was inhibited by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a selective inhibitor of protein kinase A. This block occurred at the exit of the Golgi complex, whereas transport through the Golgi compartments or from the endoplasmic reticulum to the Golgi was decreased in the presence of H-89. As judged by immunofluorescence endoplasmic reticulum to Golgi transport was accelerated in cells incubated with activators of protein kinase A such as isobutylmethylxanthine (IBMX) or forskolin (FK). Treatment with IBMX and FK also increased transport from the trans-Golgi network to the cell surface. During incubation with IBMX and FK, the organization of the Golgi complex was altered showing intercisternae fusion and miscompartmentalization of resident proteins. These structural changes affected both the kinetics of acquisition of endoglycosidase H resistance and transport activities. These data support a differential regulatory role for protein kinase A in different transport steps along the exocytic pathway. In particular, transport from the trans-Golgi network to the cell surface was dependent on protein kinase A activity. In addition, the results suggest the involvement of this enzyme on the maintenance of the Golgi complex organization.
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PMID:A regulatory role for cAMP-dependent protein kinase in protein traffic along the exocytic route. 894 80

Exocytic organelles undergo profound reorganization during myoblast differentiation and fusion. Here, we analyzed whether glycoprotein processing and targeting changed during this process by using vesicular stomatitis virus (VSV) G protein and influenza virus hemagglutinin (HA) as models. After the induction of differentiation, the maturation and transport of the VSV G protein changed dramatically. Thus, only half of the G protein was processed and traveled through the Golgi, whereas the other half remained unprocessed. Experiments with the VSV tsO45 mutant indicated that the unprocessed form folded and trimerized normally and then exited the ER. It did not, however, travel through the Golgi since brefeldin A recalled it back to the ER. Influenza virus HA glycoprotein, on the contrary, acquired resistance to endoglycosidase H and insolubility in Triton X-100, indicating passage through the Golgi. Biochemical and morphological assays indicated that the HA appeared at the myotube surface. A major fraction of the Golgi-processed VSV G protein, however, did not appear at the myotube surface, but was found in intracellular vesicles that partially colocalized with the regulatable glucose transporter. Taken together, the results suggest that, during early myogenic differentiation, the VSV G protein was rerouted into developing, muscle-specific membrane compartments. Influenza virus HA, on the contrary, was targeted to the myotube surface.
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PMID:Differential targeting of vesicular stomatitis virus G protein and influenza virus hemagglutinin appears during myogenesis of L6 muscle cells. 949 Jul 23


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